DESCRIPTION: The anterior surface of the eye functions as a barrier to the external environment and protects the delicate underlying structures from injury. This protection is provided through the elaboration of the corneal, limbal and conjunctival epithelia, as well as the meibomian gland, which contributes to the formation of the tear film. As self-renewing tissues, these epithelia are governed by stem cells, which play a crucial role in tissue homeostasis, regeneration, tissue transplantation, gene therapy, and in the pathogenesis of several anterior surface epithelial diseases. My work during the past two decades has contributed to the identification of stem cells within the corneal, conjunctival and ductal epithelial portion of the meibomian gland. Our recent data indicates that epiregulin, a potent growth factor involved in the regulation of cell proliferation and wound healing, is preferentially expressed in a subset of mouse limbal basal epithelial cells. Since corneal epithelial stem cells are located in the limbal basal epithelium, we hypothesize that epiregulin plays a key role in regulating the proliferative nature of the limbal epithelial stem cells. The long-term goal of this project is to understand the biological properties of the stem cells of the ocular surface epithelium, with a focus on the epithelial stem cells of the cornea and conjunctiva. Towards this end we will: (i) determine whether the stem cells in the ocular anterior surface epithelium divide symmetrically or asymmetrically, and to what extent can they change their mode of division;(ii) further identify and characterize stem cell-preferred molecules by transcriptional profiling the stem cell-enriched epithelia of the anterior surface;and (iii) study the role(s) of epiregulin, which is expressed in a subset of limbal epithelial basal cells, in corneal epithelial growth regulation. Data obtained from these studies should help us to understand the role of stem cells in controlling growth and differentiation of the corneal and conjunctival epithelia. These studies should form the foundation for a better understanding of the etiology of certain problems associated with limbal stem cell deficiency (e.g., persistent corneal epithelial breakdown, as well as neoplastic transformations giving rise ocular epithelial tumors).